Glyburide

Generic Name

Glyburide

Mechanism

Glyburide is a second‑generation sulfonylurea that lowers blood glucose by stimulating pancreatic β‑cell insulin release.
• Binds to the sulfonylurea receptor (SUR1) component of ATP‑sensitive K⁺ (K_ATP) channels.
• Inhibits K⁺ efflux → membrane depolarization.
• Opens voltage‑dependent Ca²⁺ channels → Ca²⁺ influx.
• Trigger exocytosis of insulin‑containing granules.
• The effect is glucose‑independent; insulin is released even at low plasma glucose, explaining the hypoglycemia risk.

Pharmacokinetics

Parameter	Details
Absorption	Rapid oral absorption; peak serum concentrations ~3–4 h post‑dose.
Distribution	Highly protein‑bound (~99 % to albumin); extensive tissue distribution.
Metabolism	Extensive hepatic CYP2C9‑mediated oxidation → inactive metabolites.
Elimination	Primarily renal excretion of metabolites; half‑life ≈10 h (dose‑dependent).
Drug Interactions	• CYP2C9 inhibitors (e.g., fluconazole, amiodarone) ↑ glyburide levels. • Sulfonylurea‑sparing agents (e.g., metformin) may reduce hypoglycemia risk.

Indications

Type 2 diabetes mellitus as monotherapy or in combination with:
Metformin
Thiazolidinediones
DPP‑4 inhibitors
GLP‑1 receptor agonists
Insulin (when titrated carefully)

> *Not indicated for type 1 diabetes, gestational diabetes, or hyperinsulinemic hypoglycemia disorders.*

Contraindications

Known hypersensitivity to glyburide or sulfonylureas.
Type 1 diabetes or ketoacidotic states.
Severe hepatic impairment (reduced metabolism, prolonged action).
Severe renal impairment (eGFR < 30 mL/min/1.73 m²) – use with caution or avoid.
Beta‑blocker therapy (risk of masking hypoglycemia).
Pregnancy & lactation – category B; avoid if possible; use insulin as first line.
Elderly – higher hypoglycemia susceptibility; start at lower dose.
Concurrent sulfonylureas or other hypoglycemics – additive risk.

Dosing

Population	Starting Dose	Titration	Max Daily Dose	Notes
Adults	5 mg PO once daily (usually 12 pm)	Increment by 5 mg every 1‑2 weeks if fasting glucose >110 mg/dL	20 mg daily	Maintain consistent food intake; avoid late dosing.
Elderly / Renal impairment	2.5 mg PO once daily	Titrate more slowly (≤1 week per step); limit to ≤10 mg daily	≤10 mg	Monitor glucose twice daily.
Children (≥10 y)	0.1 mg/kg PO once daily	<24 mg daily	20 mg daily	Not extensively studied; use cautiously.

• Administer with food to reduce GI upset.
• Do not skip doses; if missed, take next dose at routine time and do not double dose.

Adverse Effects

Hypoglycemia (most common; can be severe).
Weight gain (≈1–2 kg/month).
Dermatologic: rash, pruritus, angioedema.
Gastro‑intestinal: nausea, abdominal pain.
Rare: pancreatitis, hepatic dysfunction.
Drug interactions: Enhanced hypoglycemia with CYP2C9 inhibitors; additive weight gain with thiazolidinediones.

Monitoring

Parameter	Frequency	Rationale
Fasting/plasma glucose	Daily (self‑monitor)	Detect hypoglycemia or hyperglycemia.
HbA1c	Every 3 months	Long‑term glycemic control.
Weight	Monthly	Monitor for excessive gain.
Renal function (eGFR)	Every 6 months or at CKD onset	Dose adjustment.
Liver enzymes (ALT/AST)	Every 6 months	Detect hepatic impairment.
Electrolytes, especially K⁺	If symptomatic hypoglycemia	Uncontrolled hypoglycemia may cause electrolyte shifts.

Clinical Pearls

Start low, go slow: Initiate at 5 mg to lower the risk of prolonged hypoglycemia, especially in the elderly or those on beta‑blockers.
Timing matters: Dosing in the afternoon (12 pm) aligns drug action with post‑prandial insulin demand and reduces nocturnal hypoglycemia.
CYP2C9 genotyping: Patients with *CYP2C9* poor metabolizer status (e.g., */*) can accumulate glyburide; consider dose reduction or alternative agents.
Combination therapy: Pair glyburide with metformin to maximize efficacy while mitigating weight gain (metformin’s weight‑neutral profile).
Avoid with sulfonylurea‑sparing agents: When adding agents that also inhibit K_ATP channels (e.g., GLP‑1 agonists), monitor for additive hypoglycemia.
Surgical prep: Discontinue glyburide 1–2 days before major surgery to avoid intra‑operative hypoglycemia; consider bridging with insulin if required.
Patient education: Counsel on recognizing hypoglycemia symptoms (shakiness, diaphoresis, confusion) and proper glucagon administration if needed.

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• References

1. FDA Drug Label – Glyburide (Micromedex).

2. Goodman & Gilman's: "The Pharmacologic Basis of Therapeutics" – Sulfonylureas.

3. American Diabetes Association, Standards of Care 2024 – Pharmacologic treatment options.

4. UpToDate: "Treatment of type 2 diabetes mellitus in adults."

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• *Prepared for medical students and clinicians seeking a concise yet comprehensive reference on glyburide.*